长期服用别嘌醇缓释胶囊对高尿酸血症大鼠肾脏的影响

目的考察长期服用别嘌醇缓释胶囊对高尿酸血症大鼠肾脏改变的影响和机制。方法 90只雄性Wistar大鼠随机分为正常对照组(10只),模型组(16只),别嘌醇缓释胶囊低、高(27、54 mg·kg~(-1)·d~(-1))剂量组(各16只),别嘌醇片低、高(32、64 mg·kg~(-1)·d~(-1))剂量组(各16只),采用腺嘌呤和乙胺丁醇连续灌胃3wk,3 wk后改为隔日1次,共12 wk造成大鼠高尿酸血症。在造模的同时,药物治疗组分别给予低、高剂量的别嘌醇缓释胶囊或别嘌醇片;在wk 12末,处死大鼠,取血和肾脏组织,检测血尿酸、肾脏功能及肾组织的TNF-α表达情况和观察肾脏形态、病理学变化。结果与正常对照组比较,模型组大鼠血尿酸、尿素氮含量和肾脏组织内TNF-α表达增加,肾脏含水量显著增加(P<0.05)。与模型组比较,别嘌醇缓释胶囊高剂量组显著降低大鼠血尿酸、血尿素氮含量和肾脏组织内TNF-α表达(P<0.05);低剂量组能显著降低肾组织含水量(P<0.05);肌酐含量和肾脏指数无明显差异(P>0.05)。与别嘌醇片高剂量组比较,别嘌醇缓释胶囊组降低肾脏指数和肾组织含水量有显著差异(P<0.05,P<0.01)。结论长期应用别嘌醇缓释胶囊治疗高尿酸血症能减缓肾脏的病理改变,其机制可能与其降低血尿酸水平的同时抑制TNF-α介导的炎症反应有关。     

别嘌醇缓释微丸胶囊对高尿酸血症大鼠血液系统的影响

目的 研究长期(3个月)灌服用别嘌醇缓释微丸胶囊(ASRC)治疗大鼠高尿酸血症时对血液系统的影响.方法雄性Wistar大鼠90只,随机分为正常对照组,模型组,别嘌醇缓释微丸胶囊低、高剂量组(给予别嘌醇缓释微丸胶囊27,54 mg.kg^-1.d^-1),别嘌醇低、高剂量组(给予别嘌醇32,64 mg.kg^-1.d^-1).除正常对照组10只,其余各组增加6只,采用腺嘌呤和乙胺丁醇连续灌胃3周,3周后改为隔日一次,共12周建立大鼠高尿酸血症模型.定期检测大鼠体质量变化;12周末自动生化仪检测血尿酸(UA)水平、外周血常规;骨髓涂片检测骨髓象;ELISA方法测定大鼠血清细胞因子白细胞介素(IL)-1β水平.取肾脏组织经PAS染色,光镜观察肾脏病理结构改变.结果与正常对照组比较,高尿酸血症模型组大鼠体质量明显降低、血尿酸水平显著增高;外周血常规中白细胞(WBC)计数和血小板(PLT)计数显著增高、红细胞(RBC)计数明显降低;血清IL-1β 水平明显增高;肾脏组织内炎性细胞浸润.与模型组比较,ASRC低剂量时升高RBC计数、降低WBC、PLT计数作用显著( P<0.05),有效降低血清IL-1β水平(P<0.01);ASRC高剂量可有效抑制大鼠的体质量下降、降低血尿酸水平和血清IL-1β水平(P<0.01),肾间质仅见少量的炎性细胞浸润.结论长期应用低剂量ASRC可有效抑制高尿酸血症大鼠外周血常规的异常改变,可能与抑制炎症反应、肾脏改变轻微有关;高剂量ASRC则更好降低血尿酸水平.提示临床应用时注意药物剂量选择.     

别嘌醇缓释胶囊对高尿酸血症大鼠胃肠和皮肤的保护作用及机制

目的:考察长期(3个月)应用别嘌醇缓释胶囊对高尿酸血症大鼠胃、肠和皮肤的影响及机制。方法:60只雄性Wistar大鼠随机分为正常对照(NC)组,模型(M)组,别嘌醇缓释胶囊低(CL)、高剂量(CH)组,别嘌醇片低(TL)、高剂量(TH)组,每组10只。除NC组,其余各组采用腺嘌呤(100mg·kg-1·d-1)和乙胺丁醇(250mg·kg-1·d-1)连续灌胃3周后改为隔日1次,共12周造成大鼠高尿酸血症。药物治疗组在造模的同时,灌胃给予别嘌醇缓释胶囊或别嘌醇片,在实验第12周末,测量各组大鼠的体质量、血尿酸和血清白细胞介素(IL)-1β含量,胃、肠和皮肤的病理改变,及皮肤中肿瘤坏死因子(TNF)-α表达情况。结果:CH组可降低高尿酸血症大鼠血尿酸水平,缓解大鼠的体质量降低(P0.01);与M和TL组,特别是TH组比较,CL和CH组可缓解大鼠胃、肠黏膜损伤;与M和TL组比较,CL和CH组降低大鼠血清IL-1β水平作用显著(P0.05);CL和CH组皮肤组织中TNF-α表达明显降低。结论:与别嘌醇片比较,长期应用别嘌醇缓释胶囊在降低血尿酸的同时表现出更好的胃、肠黏膜和皮肤保护作用;抑制TNF-α及IL-1β介导的炎症反应。     

Protective Effects and Mechanisms of Allopurinol Sustained-Release Capsules on Gastrointestinal and Skin in Experimental Hyperu(ri)cacidemia Rats

目的:考察长期(3个月)应用别嘌醇缓释胶囊对高尿酸血症大鼠胃、肠和皮肤的影响及机制.方法:60只雄性Wistar大鼠随机分为正常对照(Nc)组,模型(M)组,别嘌醇缓释胶囊低(CL)、高剂量(CH)组,别嘌醇片低(TL)、高剂量(TH)组,每组10只.除Nc组,其余各组采用腺嘌呤(100 mg·kg-1·d-1)和乙胺丁醇(250 mg· kg-1· d-1)连续灌胃3周后改为隔日1次,共12周造成大鼠高尿酸血症.药物治疗组在造模的同时,灌胃给予别嘌醇缓释胶囊或别嘌醇片,在实验第12周末,测量各组大鼠的体质量、血尿酸和血清白细胞介素(IL)-1β含量,胃、肠和皮肤的病理改变,及皮肤中肿瘤坏死因子(TNF)-α表达情况.结果:CH组可降低高尿酸血症大鼠血尿酸水平,缓解大鼠的体质量降低(P＜0.01);与M和TL组,特别是TH组比较,CL和CH组可缓解大鼠胃、肠黏膜损伤;与M和TL组比较,CL和CH组降低大鼠血清IL-1β水平作用显著(P＜0.05);CL和CH组皮肤组织中TNF-α表达明显降低.结论:与别嘌醇片比较,长期应用别嘌醇缓释胶囊在降低血尿酸的同时表现出更好的胃、肠黏膜和皮肤保护作用;抑制TNF-α及IL-1β介导的炎症反应.     

别嘌醇改善果糖诱导的大鼠高尿酸血症与调节肠道葡萄糖转运子表达的关系研究

目的观察别嘌醇和苯溴马隆对高果糖饮水诱导的高尿酸血症(hyperuricemia,HUA)大鼠血尿酸水平、肝脏黄嘌呤氧化酶活性以及肠道果糖转运子(glucose transporter,GLUT)2和5表达的影响。方法 Wistar大鼠连续饮用10%果糖水8周以制备高尿酸血症大鼠模型,其中从第5周开始分别给予大鼠灌胃5 mg·kg~(-1)别嘌醇或10 mg·kg~(-1)苯溴马隆,共4周。磷钨酸法检测大鼠血尿酸水平,比色法检测肝脏XOD活性,Western blot法和免疫组化染色法检测肠道GLUT2和GLUT5的表达。结果别嘌醇明显降低果糖诱导的HUA大鼠血尿酸水平(P<0.01)和肝脏XOD活性(P<0.01),减少了HUA大鼠肠道GLUT5的表达(P<0.01),但对肠道GLUT2的表达无明显影响。与此同时,苯溴马隆也明显降低了果糖诱导的HUA大鼠血尿酸水平(P<0.01),但对HUA大鼠肝脏XOD活性、肠道GLUT2和GLUT5的表达均无明显影响。结论别嘌醇可明显降低果糖诱导的HUA大鼠血尿酸水平,其机制与抑制肝脏XOD活性以减少尿酸产生,抑制GLUT5表达以减少肠道果糖转运吸收,最终减少果糖代谢产生尿酸相关。     

别嘌醇缓释微丸的研制

目的:制备别嘌醇缓释微丸,考察其释药机制.方法:采用正交试验法进行处方筛选优化,用数学模型拟合释放曲线.结果:微晶纤维素(MCC)的用量对微丸的成球性、释药速率有显著的影响,别嘌醇缓释微丸的体外释药行为符合Higuchi方程释放模型.结论:制备别嘌醇缓释微丸具有较好的缓释效果.     

苯溴马隆与别嘌醇治疗高尿酸血症的疗效比较

目的比较苯溴马隆和别嘌醇对高尿酸血症和痛风患者的降尿酸临床疗效和安全性。方法66例30～65岁的高尿酸血症和痛风患者（男性46例,女性20例）,随机分为苯溴马隆治疗组（34例）和别嘌醇治疗组（32例）,分别服用苯溴马隆片50mg／d和别嘌醇300mg／d,疗程均为4周。以治疗后血尿酸降低值和降低百分率来判断疗效。并观察治疗期间有无痛风发作及用药前后血常规、尿蛋白、肝功能及肾功能的变化。结果苯溴马隆和别嘌醇均可有效控制血尿酸水平,总有效率分别为97．1％和90．6％（P〉0．05）。别嘌醇组用药后出现白细胞和血小板明显下降（P〈0．05）,转氨酶明显升高（P〈0．05）;苯溴马隆组用药前后以上指标无明显变化（P〉0．05）。两组肾功能和尿蛋白均无明显变化。结论苯溴马隆用于治疗高尿酸血症和痛风患者是有效、安全而方便的选择。     

芒果苷对氧嗪酸钾所致慢性高尿酸血症大鼠尿酸及肝肾功能的影响

目的研究芒果苷对氧嗪酸钾所致慢性高尿酸血症大鼠尿酸及肝肾功能的影响。方法连续灌胃给予SD大鼠氧嗪酸钾(2.5 g·kg-1体重)复制慢性高尿酸血症大鼠模型。以苯溴马隆和别嘌醇为阳性对照,研究芒果苷灌胃给药5周对高尿酸血症大鼠血尿酸(uric acid,UA)、肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)、谷丙转氨酶(ALT)、γ-谷氨酰转肽酶(GGT)、谷草转氨酶(AST)等水平的影响。结果芒果苷(1.55和3.13 mg·kg-1)灌胃给药能剂量依赖性地降低氧嗪酸钾所致的慢性高尿酸血症大鼠的血清尿酸水平,其效价弱于别嘌醇,但不亚于苯溴马隆;对肌酐、尿素氮和尿量的影响不明显,对血清AST、GGT水平亦无明显影响,但可改善慢性高尿酸血症大鼠的血清ALT水平。结论芒果苷可降低氧嗪酸钾所致慢性高尿酸血症大鼠的尿酸水平,对肝肾功能无明显影响。     

阿托伐他汀联合别嘌醇对高脂血症合并高尿酸血症患者血脂血尿酸的影响

目的 探讨阿托伐他汀联合别嘌醇对高脂血症合并高尿酸血症患者血脂和血尿酸的影响.方法 将102例高脂血症合并高尿酸血症患者随机均分为A、B、C三组,每组34例.A组患者给予阿托伐他汀钙片与别嘌醇片,B组患者给予阿托伐他汀钙片,C组患者给予别嘌醇片,各组疗程均为4周.观察各组患者治疗前后甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、尿酸(UA)、丙氨酸转氨酶(ALT)、肌酸磷酸激酶(CK)、尿素氮(BUN)水平及不良反应.结果 治疗后,各组患者TG、TC、LDL水平均显著低于同组治疗前,且A、B组低于C组;各组患者UA水平均显著低于同组治疗前,且A、B组低于C组,A组低于B组;A、B组患者ALT水平、各组患者CK水平和A、C组患者BUN水平均高于同组治疗前,且A、B组CK水平高于C组,A组高于B组,差异有统计学意义(P＜0.05);BUN水平B组患者治疗前后及各组间比较差异无统计学意义(P＞0.05).治疗期间,A组有1例(2.94％)患者出现胃肠道反应,无痛风发作;B组有3例(8.82％)患者出现胃肠道反应,无痛风发作;C组有4例患者出现胃肠道反应,2例出现痛风发作,不良反应率为17.65％.结论 阿托伐他汀联合别嘌醇可显著降低高脂血症合并高尿酸血症患者血脂、UA水平,且安全性较好.     

苯溴马隆与别嘌醇治疗高尿酸血症临床效果对照

目的：观察苯溴马隆(立加利仙)及别嘌醇对高尿酸血症的疗效。方法：48例患者，随机分为两组，分别口服苯溴马隆(立加利仙)50mg(每日1次)及别嘌醇100mg(每日1次)进行治疗。结果：临床疗效观察及血尿酸测定表明，苯溴马隆(立加利仙)治疗组明显优于别嘌醇治疗组。结论：苯溴马隆(立加利仙)治疗高尿酸血症疗效更为显著、可靠。     

松叶提取物对“过食膏粱厚味”型高尿酸血症大鼠尿酸生成排泄、肝功能及血脂水平的影响

目的 研究松叶提取物对“过食膏粱厚味”型高尿酸血症大鼠尿酸生成排泄、肝功能及血脂水平的影响。方法 将60只♂SD大鼠,随机分为正常对照组、模型对照组、别嘌醇（0.01 g·kg^-1）阳性对照组、松叶提取物3个剂量组（10.0,5.0,2.5 g·kg^-1）,每组10只。除正常对照组给予等体积蒸馏水,其余各组每天上午灌胃给予脂肪乳剂造模,下午灌胃给药,连续9周。观察大鼠一般行为学、摄食量、体质量,分别检测大鼠血清SUA、SCR、BUN、ALT、AST、TC、LDL-c含量;收集24 h尿液,记录UV,检测大鼠尿UUA、UCR含量,计算24 h UUA、FEUA、CUr、CCr,末次给药后测定血清和肝脏XOD、ADA、HGPRT活性。结果 模型对照组大鼠体质量明显降低,血清SUA、SCR、BUN、ALT、TC、LDL-c水平以及血清和肝组织XOD、ADA活性显著升高,肝组织HGPRT活性显著降低,同时UUA、UCR、UV、24 h UUA、FEUA、CUr、CCr显著降低。松叶提取物能显著降低高尿酸血症大鼠血清SUA、SCR、BUN、ALT、TC、LDL-c水平,降低血清和肝组织XOD、ADA活性,升高肝组织HGPRT活性,并且升高UUA、UCR、UV、24 h UUA、FEUA、CUr、CCr。结论 松叶提取物能有效降低HUA大鼠尿酸的生成并促进其排泄,且具有保肝、调血脂的功能。     

Morin reduce uric acid level in hyperuricemia mice

OBJECTIVE To explore morin's effect on hyperuricemia mice. METHODS Mice were grouped as control, model, morin low dose, middle dose, high dose,allopurinol, benzbromarone. Hyperuricemia model was built by 300 mg · kg~(-1) potassium oxonate intraperitoneal injection. After model built, administrated morin two weeks and sampled serum, kidneys, ileum and liver. Assay UA, BUN, CRE, AST, ALT, TG, CHO, ALB, HDL, LDL by Biochemical analyzer. RESULTS Morin groups can reduce the serum uric acid. Compared with allopurinol,morin have less BUN level and CRE level in serum. Morin can reduce ALT level and high dose of morin group significantly reduce LDH level. CONCLUSION morin can reduce the serum uric acid on hyperuricemia mice, meanwhile, has liver and kidneys protective effects in some degrees.     

Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.     

Effect of glycine on tissue fatty acid composition in an experimental model of alcohol-induced hepatotoxicity

1. The aim of the present study was to investigate the effect of the administration of glycine, a non-essential amino acid, on blood alcohol levels and tissue fatty acid composition in experimental rats. 2. Liver cell damage was induced by the administration of ethanol (7.9 g/kg bodyweight) for 30 days by intragastric intubation. Control rats were given isocaloric glucose solution. Glycine was subsequently administered at a dose of 0.6 g/kg bodyweight every day by intragastric intubation for the next 30 days. 3. Feeding alcohol significantly elevated the activities of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatases (ALP) and gamma-glutamyl transpeptidase (GGT) and altered the liver and brain fatty acid composition compared with control rats. Subsequently, glycine supplementation to alcohol-fed rats significantly lowered the activities of serum AST, ALT, ALP, GGT and normalized the liver and brain fatty acid composition compared with untreated alcohol-fed rats. 4. Thus, the present study demonstrates that oral administration of glycine confers a significant protective effect against alcohol-induced hepatotoxicity by virtue of its ability to optimize the activities of serum AST, ALT, ALP and GGT, as well as the tissue fatty acid composition.     

茶黄素对高尿酸血症小鼠的降尿酸作用研究

目的 研究茶黄素对高尿酸血症模型小鼠的降尿酸作用.方法 采用氧嗪酸钾诱导高尿酸血症小鼠模型,茶黄素低、中、高剂量(6、20、60 mg/kg)和别嘌呤(10 mg/kg)连续ig给药7 d,检测高尿酸血症小鼠血清尿酸(UA)、尿素氮(BUN)、肌酐(CRE)、天冬氨酸氨基转氨酶(AST)、丙氨酸氨基转氨酶(ALT)水平...     

北豆根不同组分多次给药对小鼠肝毒性“量-时-毒”关系研究

目的研究北豆根不同组分多次给药对小鼠肝毒性"量-时-毒"关系的影响。方法小鼠按不同时间点或不同剂量分组,给小鼠灌胃北豆根水提和醇提组分,每天1次,连续灌胃7天,观察给药后小鼠死亡情况和毒性反应,分别于药后1、3、7天检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST),血浆清蛋白(ALB)、血清碱性磷酸酶(ALP)、胆红素(TBI)水平,并计算肝脏指数。结果北豆根水提组分和醇提组分可致血中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性增高,ALT、AST在给药后1天明显升高,以AST为更敏感,一直持续到7天。肝脏重量和肝体比值增大,血清碱性磷酸酶(ALP)、胆红素(TBI)水平增加,血浆清蛋白(ALB)降低;上述变化随给药次数和剂量的增加而逐渐加重,呈现一定的时间、剂量依赖性。结论小鼠多次灌胃给予一定剂量的北豆根水提组分或醇提组分可造成明显的肝毒性损伤,即肝功指标的改变,并呈现一定的"量-时-毒"关系。关于其肝脏损伤的机制有待进一步研究。     

Biochemical changes in the kidney and liver of rats following administration of ethanolic extract of Psidium guajava leaves

Furtherance to a previous report on the anti-trypanosomal properties of Psidium guajava aqueous leaf extract in rats experimentally infected with Trypanosoma brucei brucei, we have evaluated the effects of the daily intraperitoneal administration of P. guajava leaf extract to rats on the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) in the kidney, liver and serum. The results obtained revealed that the administration of the extract produced significant increase in the serum activities of AST, ALT, ALP and ACP when compared with the control (p < 0.05). Also AST, ALT and ALP and ACP activities in the tissues of animals administered the extract revealed inconsistent changes (p < 0.05) relative to control. The increase in the serum activity of ALP may be an indicator that there was a likely compromise to the integrity of the plasma membrane as a result of the ethanolic extract administration. This could have caused leakages of the other enzymes investigated, which may explain the corresponding increases in the serum activities of AST, ALT and ACP observed.     

Effect of ascorbic acid supplementation on liver and kidney toxicity in cyclophosphamide-treated female albino rats.

Effects of ascorbic acid supplementation on the activity of acid phosphatase (ACP), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) on liver, kidney and serum in cyclophosphamide-treated female virgin rats were investigated. Oral administration of cyclophosphamide at the dose of 5 mg/kg body weight/day for 12 days resulted in a significant elevation in ACP and ALP activities in liver, kidney and serum. Ascorbic acid supplementation at the dose of 25 mg/kg body weight/day showed a significant protection in the activity of ACP in liver, kidney and serum, but only in ALP activity in kidney. ALP activities in liver and serum were not restored to control level by ascorbic acid supplementation. Activities of GOT and GPT were elevated significantly in liver, kidney and serum after cyclophosphamide treatment, and were protected and restored to control level by ascorbic acid supplementation.     

别嘌呤醇降低血尿酸水平以控制慢性肾病进展的研究

目的:探讨用别嘌呤醇降低血清尿酸水平以控制高尿酸血症慢性肾病进展。方法:将47例慢性肾病合并高尿酸血症患者随机分为治疗组与对照组,治疗组在对照组抗高血压药治疗的基础上给予别嘌呤醇100~200mg.d-1或通常疗法治疗12mo。结果:治疗组血清肌酐水平较对照组低,肾功能恶化者较对照组明显下降(P<0.05)。结论:别嘌呤醇可保护肾功能,安全、有效。